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Biomedical subjects

Giovanni B Frisoni

Publications and source records attributed to Giovanni B Frisoni.

At least 37 records · Page 2Linked to original sources
PubMed2005

Frontotemporal dementia as a neural system disease.

Some brain structures atrophic in frontotemporal dementia (FTD) belong to the rostral limbic system (RLS), that regulates context-dependent behaviors after evaluation of the motivational content of stimuli. The clinical manifestations of FTD are consistent with its impairment. Aim of this study was to assess whole brain morphology in FTD using magnetic resonance imaging (MRI) and voxel-based morphometry with statistic parametric mapping (SPM99) to test the hypothesis that the RLS might be specifically targeted by FTD. Nine FTD patients and 26 healthy controls underwent high resolution 3D MRI. SPM99 performed (a) spatial normalization to a customized template, (b) segmentation, (c) smoothing, (d) voxel-by-voxel comparison of gray matter between cases and controls. P was set at 0.05 corrected for multiple comparisons. All but one regions of the RLS (the periaqueductal gray) were atrophic in FTD. At P<0.001 uncorrected also the periaqueductal gray was atrophic. Atrophy outside the RLS was confined to a few voxels in the frontal and temporal gyri. FTD might be a neural-system disease where the RLS is predominantly damaged.

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PubMed2005

Relationship between functional loss before hospital admission and mortality in elderly persons with medical illness.

OBJECTIVE: This hospital-based prospective study tests the hypothesis that, in a large group of hospitalized elderly patients, those who report functional decline between pre-illness baseline and hospital admission have a higher risk of death. METHODS: Nine hundred fifty elderly ambulant patients (F = 69.3%; mean age 78.3 +/- 8.5 years) were consecutively admitted to a geriatric ward (Poliambulanza Hospital, Brescia, Italy) during a 15-month period. Number and severity of somatic diseases, Charlson Index score, APACHE II score, level of serum albumin, cognitive status (by Mini-Mental State Examination), and depression score (by Geriatric Depression Scale), were assessed on admission and evaluated as potential prognostic factors. Functional status (by Barthel Index) was assessed by self-report on admission. Preadmission function was also assessed by self-report at the time of admission. Impairment of function due to an acute event is measured as the difference between performances on admission and 2 weeks before the acute event. Six-month survival was the main outcome variable. RESULTS: Factors related to mortality in bivariate analysis were: male sex, age over 80, cancer, congestive heart failure, pulmonary diseases, elevated Charlson Index score, and (independently) dementia (Mini-Mental State Examination < 18), APACHE-Acute Physiology Score , albumin level <3.5 g/dL, and anemia. After controlling for these variables and for Barthel Index score 2 weeks before the acute event, change in function due to the acute disease is independently related to 6-month mortality (minor functional change [<30 Barthel Index Point] relative risk: 1.3, 95% confidence interval, 0.6-3.0 and major functional change [major functional decrement] relative risk: 2.8, 95% confidence interval, 1.3-5.7). CONCLUSIONS: Disease-induced disability may reflect a condition of biological inability to react to acute diseases (i.e., frailty), and should be assessed as a relevant prognostic indicator.

Activities of Daily Living↗
PubMed2005

Reality orientation therapy combined with cholinesterase inhibitors in Alzheimer's disease: randomised controlled trial.

BACKGROUND: Reality orientation therapy combined with cholinesterase inhibitors has not been evaluated in patients with Alzheimer's disease. AIMS: To perform such an evaluation. METHOD: We randomly assigned 79 of 156 patients treated with donepezil to receive a reality orientation programme. Caregivers of the treatment group were trained to offer the programme at home 3 days a week, 30 min/day, for 25 consecutive weeks, and were invited to stimulate and involve patients in reality-based communication. RESULTS: The treatment group showed a slight improvement in Mini-Mental State Examination (MMSE) scores (mean change +0.2, s.e.=0.4) compared with a decline in the control group (mean change -1.1, s.e.=0.4; P=0.02). Similarly for the Alzheimer's Disease Assessment Scale--Cognition (treatment group mean change +0.4, s.e.=0.8; control group -2.5, s.e.=0.8; P=0.01). The intervention had an equal effect on cognition in those with mild (MMSE score > or = 20) and moderate (score <20) dementia. No significant effect was observed for behavioural and functional outcomes. CONCLUSIONS: Reality orientation enhances the effects of donepezil on cognition in Alzheimer's disease.

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PubMed2004

Pathological validation of a CT-based scale for subcortical vascular disease. The OPTIMA Study.

The validity of a computed tomography (CT)-based rating scale that separately rates leukoaraiosis, patchy lesions, and lacunes was tested using neuropathological findings collected on 87 subjects enrolled in the Oxford Project to Investigate Memory and Ageing. The CT-based score (range 0-64) was associated with both small vessel disease (p = 0.015) and microinfarcts (p = 0.002) on pathology. A sum score of subcortical cerebrovascular disease (CVD) on pathology was computed, 0 indicating absent/mild small vessel CVD and no microinfarcts, 1 moderate small vessel CVD or microinfarcts, and 2 and higher both conditions or severe small vessel CVD. Subjects with a sum score of 0 were decreasing with increasing severity of CT-based score (64, 46, and 25% in those with CT-based scores of 0, 1-38, and 39 and higher), while those with a sum score of 2 and higher were increasing (0, 14, and 44%; p = 0.002). A standardized assessment of subcortical CVD on CT films can be compounded into a unique score that is in good agreement with neuropathology. This supports the validity of the CT-based visual rating scale as a valid tool to detect subcortical vascular changes in elderly persons.

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PubMed2004

Differential associations of Head and Body Symptoms with depression and physical comorbidity in patients with cognitive impairment.

OBJECTIVE: To test the hypothesis that physical symptoms referred to the head might be specifically associated with depression in patients with cognitive impairment. METHODS: Subjects were taken from those enrolled in 'The Mild Project' a prospective study on the natural history of mild dementia (Mini Mental State Examination > or = 18) and with a diagnosis of Alzheimer's disease, vascular dementia, and mild cognitive impairment. A total of 129 subjects were included in the study. Physical symptoms were assessed with a checklist investigating nine different body organs or apparati. Physical symptoms were grouped into those referred to the head (Head Symptoms: ear and hearing; eyes and sight; and head and face) and all the others (Body Symptoms). Depressive symptoms were assessed with the Geriatric Depression Scale (GDS) and physical comorbidity with Greenfield's Index of Disease Severity (IDS). RESULTS: The number of patients reporting one or more Head Symptoms linearly increased with increasing depression severity (Mantel-Haenszel test = 6.497, df = 1, p = 0.011), while the number of patients reporting one or more Body Symptoms linearly increased with increasing physical comorbidity (Mantel-Haenszel test = 4.726, df = 1, p = 0.030). These associations were confirmed in multivariate logistic regression models with adjustment for potential confounders (age, gender, education, cognitive performance, daily function, and diagnosis). CONCLUSIONS: Head Symptoms are specifically associated with depression while Body Symptoms with physical comorbidity, in patients with cognitive impairment. Recognizing these associations in individual patients may help clinicians decide whether to initiate or continue antidepressant therapy or whether to carry out physical instrumental investigations.

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PubMed2004

Association between subcortical vascular disease on CT and neuropathological findings.

BACKGROUND: Small vessel cerebrovascular disease (svCVD) causes cognitive impairment and predicts poorer outcomes in elderly persons. The demonstration of svCVD by structural imaging such as computed tomography (CT) is central to the clinical diagnosis but its accuracy is uncertain. OBJECTIVE: The aim of this study was to assess the validity of CT to detect pathologically verified svCVD. METHODS: Leukoaraiosis, patchy lesions, and lacunes were assessed separately in different cerebral regions on CT scans of 87 elderly persons with Mini-Mental State Examination scores between 0 and 30 enrolled in the OPTIMA project. We rated small vessel disease on pathology separately in the white matter and basal ganglia as absent/mild, moderate, and severe. The presence of microinfarcts was also noted. RESULTS: The severity of all types of CT lesions was associated with pathological findings. Subjects with absent/mild leukoaraiosis on CT decreased and those with severe leukoaraiosis increased with increasing severity of subcortical small vessel ratings on pathology (31, 18 and 0%; 17, 23 and 50%, respectively; p = 0.028). A similar association was present for patchy lesions (73, 59 and 17%; 7, 18 and 33%, respectively; p = 0.004) and lacune (83, 77 and 50%; 0, 4 and 17%, respectively; p = 0.023). Leukoaraiosis, patchy lesions, and lacunes on CT were associated also with microinfarcts on pathology (p < 0.05). CONCLUSION: The standardized assessment of svCVD on CT films at the time of the diagnosis correlates with small vessel disease on pathology at death.

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PubMed2004

A comparison between the accuracy of voxel-based morphometry and hippocampal volumetry in Alzheimer's disease.

PURPOSE: To compare the accuracy of voxel-based morphometry (VBM) and region of interest (ROI)-based hippocampal volumetry to detect medial temporal lobe atrophy in Alzheimer's disease (AD). MATERIALS AND METHODS: A total of 27 AD patients (age 74 +/- 9 years; 22 women; Mini-Mental State Exam [MMSE] 21 +/- 4) and 25 controls (age 70 +/- 8; 16 women; MMSE 29 +/- 1) were studied. Accuracy of VBM to detect gray matter loss in those seven AD patients and 11 controls with similar ROI-based hippocampal measures and of ROI-based volumetry to detect gray matter loss in those four AD patients and five controls with similar VBM-based hippocampal measures was assessed. VBM was performed with statistical parametric mapping (SPM99). RESULTS: The area under the curve was 0.96 (95% C.I., 0.92-1.00) for VBM, 0.89 (95% C.I., 0.80-0.98) for ROI-based hippocampal measures, and 0.99 (95% C.I., 0.96-1.00) for both. In subjects with similar ROI-based hippocampal measures, VBM detected atrophy in AD patients at P < 0.0001, while in subjects with similar VBM-based hippocampal measure, volumetry was not significant (P = 0.11). Both measures independently contributed to discrimination (P = 0.004 and P = 0.032) in a logistic regression model. CONCLUSION: These results indicate that VBM is more accurate, but the combination of both methods provides the highest accuracy for detection of hippocampal atrophy in AD.

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PubMed2004

Blunted reduction in night-time blood pressure is associated with cognitive deterioration in subjects with long-standing hypertension.

OBJECTIVE: Data about the relationship of blunted reduction of night-time blood pressure (BP) with cognitive deterioration (CD) are conflicting. This study aims to explore this possible association in elderly people with long-standing hypertension. METHODS: Twenty-six hypertensive subjects consecutively admitted to a rehabilitation unit over a six-month period were recruited. Exclusion criteria concerned all clinical conditions potentially related to BP variability or leading to CD. All patients underwent a clinic and 24-h BP non-invasive monitoring assessment of BP, as well as a cognitive assessment with the Mini Mental State Examination (MMSE). The presence of cerebrovascular disease (CVD) was assessed on CT films, with a standardized visual rating scale. RESULTS: Blunted reduction of both systolic and diastolic night-time BP were significantly associated with poorer cognitive performances (r=0.61, p=0.001 for systolic; and r=0.57, p=0.002 for diastolic, respectively). In a multiple regression model, blunted reduction of night-time BP (B=0.17, [95% confidence intervals: 1.1-1.3], p=0.008 for systolic; and B=0.15, [95% confidence intervals: 1.0-1.3], p=0.02 for diastolic) independently predicted poorer cognitive performances. CONCLUSIONS: In subjects with long-standing hypertension the blunted reduction of night-time BP is independently associated with lower cognitive performances.

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PubMed2004

Subcortical vascular lesions predict functional recovery after rehabilitation in patients with L-dopa refractory parkinsonism.

OBJECTIVES: To identify predictors of functional recovery after an intensive rehabilitation training in patients with gait disturbances and refractory parkinsonism. DESIGN: Observational study. SETTING: A hospital geriatric rehabilitation department ("Ancelle della Carità" hospital of Cremona). PARTICIPANTS: Thirty-eight subjects (mean age+/-standard deviation of 78.9+/-6.5; 66% women) with gait disturbances and L-dopa refractory parkinsonism consecutively admitted to a rehabilitation unit within 6 months were recruited. Exclusion criteria were obvious musculoskeletal disorders (severe leg arthritis, hemiparesis, recent stroke), recent surgery, delirium, physical impairment from other identifiable causes, and missing computed tomography (CT) scan. All subjects received an intensive standardized rehabilitative program including conventional physical therapy and specific gait training. MEASUREMENTS: The outcome measure of the rehabilitation training was the gain between admission and discharge on the Unified Parkinson Disease Rating Scale (delta-UPDRS). The following potential predictors were assessed using comprehensive geriatric assessment: physical health (Charlson Comorbidity Index, number of drugs), cognitive performance (Mini-Mental State Examination (MMSE)), functional status (Tinetti scale), depressive symptoms (Geriatric Depression Scale), nutritional status (serum albumin and body mass index), and subcortical cerebrovascular load (four classes of increasing severity based on diffuse leukoariosis, patchy lesions of the white matter, and lacunas on CT scan). Multivariate logistic regression with fixed adjustment for age, cognitive performance, and UPDRS on admission and stepwise selection of variables were used to identify independent predictors. RESULTS: Patients were divided into two groups of equal size based on the delta-UPDRS (high and low functional recovery: delta-UPDRS >8 and </=8, respectively). Of all variables, only subcortical cerebrovascular load predicted functional recovery at discharge (odds ratio adjusted for age, MMSE, and UPDRS on admission=2.3, 95% confidence interval=1.0-5.1). The adjusted proportion of patients with high functional recovery decreased with increasing subcortical cerebrovascular load: 83%, 61%, 44%, and 27% (adjusted P for trend=0.047). CONCLUSION: Subcortical cerebrovascular load is a predicting factor of successful rehabilitation in patients with L-dopa refractory parkinsonism.

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PubMed2003

Computer-assisted imaging to assess brain structure in healthy and diseased brains.

Neuroanatomical structures may be profoundly or subtly affected by the interplay of genetic and environmental factors, age, and disease. Such effects are particularly true in healthy ageing individuals and in those who have neurodegenerative diseases. The ability to use imaging to identify structural brain changes associated with different neurodegenerative disease states would be useful for diagnosis and treatment. However, early in the progression of such diseases, neuroanatomical changes may be too mild, diffuse, or topologically complex to be detected by simple visual inspection or manually traced measurements of regions of interest. Computerised methods are being developed that can capture the extraordinary morphological variability of the human brain. These methods use mathematical models sensitive to subtle changes in the size, position, shape, and tissue characteristics of brain structures affected by neurodegenerative diseases. Neuroanatomical features can be compared within and between groups of individuals, taking into account age, sex, genetic background, and disease state, to assess the structural basis of normality and disease. In this review, we describe the strengths and limitations of algorithms of existing computer-assisted tools at the most advanced stage of development, together with available and foreseeable evidence of their usefulness at the clinical and research level.

Algorithms↗
PubMed2003

Drug treatment of REM sleep behavior disorders in dementia with Lewy bodies.

BACKGROUND: Dementia with Lewy bodies (DLB) is often associated with REM sleep behavior disorders (RBD) characterized, in contrast to the usual paralysis of REM sleep, by violent motor and verbal activity. PATIENTS AND METHODS: The pharmacological management of RBD was investigated in three DLB patients treated with clonazepam, a benzodiazepine used as an antiepileptic, or donepezil, a cholinesterase inhibitor. RESULTS: All three patients had marked improvement. The pharmacodynamic mechanisms underlying the efficacy of the two drugs might be due to facilitator effect on the pedunculopontine nucleus, a key structure in the physiology of REM sleep.

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PubMed2003

Mild cognitive deterioration with subcortical features: prevalence, clinical characteristics, and association with cardiovascular risk factors in community-dwelling older persons (The InCHIANTI Study).

OBJECTIVES: To identify subjects with minimal or mild nonamnestic cognitive impairment with parkinsonian stance and gait and investigate vascular correlates of this condition. DESIGN: First wave of an epidemiological longitudinal study (InCHIANTI) on factors predicting loss of mobility in older persons. SETTING: The Chianti geographic area (Tuscany, Italy). PARTICIPANTS: Five hundred fifty-six subjects aged 70 to 90 with Mini-Mental State Examination (MMSE) scores greater than 23 of 30, of the 1,260 persons aged 65 and older randomly selected from the population registry of Greve in Chianti and Bagno a Ripoli, two small towns near Florence. METHODS: Low cognitive performance (LCP) was defined as an age- and education-adjusted MMSE below the 50th percentile for the InCHIANTI population. Subcortical features were plastic rigidity on neurological examination (parkinsonism), gait disturbance (small-step gait or parkinsonian gait), and dysexecutive features. Two hundred forty-three participants had high cognitive performance, 166 had LCP without subcortical features, and 75 had LCP with subcortical features. Vascular risk factors were hypertension, atrial fibrillation or pathological findings on electrocardiogram (ECG), low serum high-density lipoprotein (HDL) or high low-density lipoprotein cholesterol, diabetes mellitus, obesity, and heavy smoking. RESULTS: Three main vascular risk factors were significantly more prevalent in LCP with subcortical features: hypertension (P =.02), atrial fibrillation or ECG changes (P =.04), and low HDL cholesterol (P =.001). LCP with subcortical features was significantly associated with cerebrovascular risk factors (P =.001). CONCLUSION: Gait disturbance and nonamnestic cognitive symptoms might be the consequence of subcortical vascular damage.

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PubMed2003

Validation study of a CT-based weighted rating scale for subcortical ischemic vascular disease in patients with mild cognitive deterioration.

OBJECTIVES: Subcortical ischemic vascular disease (SIVD) is frequently associated with cognitive impairment. Rating scales to grade cerebrovascular disease are available, but their sensitivity to the clinical features of mild SIVD is unclear. The aim of the study is to devise and validate a computed tomography (CT)-based visual rating scale sensitive to SIVD in patients with mild cognitive deterioration. METHODS: Subjects were 122 consecutive outpatients of a memory clinic (mean age +/- SD 77 +/- 8 years, 71% females, mean +/- SD score of mental state exam 22 +/- 3, 61% with clinical dementia rating of 0.5 and 39% of 1). Diffuse leukoaraiosis, fuzzy and patchy lesions, and lacunes were assessed on ordinary CT films and weights were computed based on clinical indicators of SIVD. A continuous score and an ordinal class (0-3) with higher values indicating higher vascular damage were derived. RESULTS: Intraclass correlation coefficients for intra- and interrater reliability of the subcortical vascular score and class ranged from 0.84 to 0.88. Convergent validity versus the scale of Wahlund et al. was good (Spearman's correlation coefficient between 0.53 and 0.73, p < 0.0005). Known-group validity was assessed versus clinical diagnoses of degenerative (mild cognitive impairment determined by Petersen et al. and NINCDS-ADRDA probable Alzheimer's disease; n = 58), mixed (possible Alzheimer's disease with cerebrovascular disease; n = 21), and vascular cognitive impairment (criteria of Erkinjuntti et al. for subcortical vascular dementia and cognitive impairment; n = 43). Patients with degenerative cognitive impairment were more often in the lower subcortical vascular classes (43% in class 0, 43% in class 1, 14% in class 2, and 0% in class 3), while patients with mixed (0, 24, 24, and 52%) and vascular cognitive impairment were in increasingly higher subcortical vascular classes (0, 12, 35, 53%; p < 0.00005). Criterion-related validity was assessed versus clinical indicators of cerebrovascular disease. Hypertension, platelet aggregation inhibitor use, balance, gait, and bradykinesia increased linearly with increasing subcortical vascular class (p for trend <0.02). CONCLUSIONS: This rating scale is valid and sensitive to capture different degrees of SIVD associated with mild cognitive deterioration.

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